History of Molecular Genetics Friedrich Miescher • In 1869 extracted a viscous white substance from the nucleus of a cell • Substance was slightly acidic and rich in phosphorous and nitrogen • Named it nuclein because it was found in the nucleus Frederick Griffith • In 1920s tried to develop a vaccine against pneumonia • Discovered transformation Joachim Hammerling • In 1930s studied one-celled green alga Acetabularia to determine the location of DNA within the cell Oswald Avery, Maclyn McCarty and Colin McLeod • In 1944 Avery and colleagues continued the work of Griffith • Ruptured heat-killed encapsulated cells to release their content. Each component (DNA, RNA, protein) was isolated and tested for transforming ability • Determined that protein is not the hereditary material but instead DNA is the material of which genes and chromosomes are made Erwin Chargaff •In 1950s studied DNA in many different organisms •The proportion of Adenine in a DNA molecule is equal with to that Thymine, and the proportion of Guanine is equal to that of Cytosine • Found that the composition of DNA varies from one species to another, in particular in the relative amounts of A, G, T, and C bases • Helped lead to the discovery of the double helix structure of DNA Alfred Hershey & Martha Chase • In 1952 found virus infects a bacterial host by attaching to the surface of the cell and injecting its DNA into the cell. This produced 1000s of new viruses which burst out of the cell, resulting in cell death • Results: only the DNA (rich in phosphorus) from the virus, not the protein (rich in sulfur), enters the bacteria to direct the synthesis of new viruses (reproduction) Rosalind Franklin • In 1953 with her student Raymond Gosling, discovered that there were two forms of DNA – when wet, the DNA fibre became long and thin – when it was dried it became short and fat • Discovered that the sugar-phosphate backbone of DNA lies on the outside of the molecule, not the inside as was previously thought • Could not discover from her data was how the bases paired on the inside of helix, for which James Watson and Francis Crick had the answer James Watson & Francis Crick • In 1950s put the last piece of DNA structure together from a variety of sources including Franklin and Chargaff – Rosalind Franklin was friendly with Watson & Crick, and communicated regularly with them until her life and career were cut short by cancer in April of 1958, at the age of 37 Matthew Meselson & Franklin Stahl • In 1958 discovered that DNA replication is semiconservative: ½ of the double helix is old; ½ is new) Human Genome Project • $3 billion project began in 1990 by the United States Department of Energy and the U.S. National Institute of Health and was expected to take 15 years • Comprised of 1000s of geneticists from around the world • A working draft of the genome was announced in 2000 and a complete one in 2003, with further, more detailed analysis still being published • The ultimate goal was to “understand the human genome” and gain “knowledge of the human as necessary to the continuing progress of medicine and other health sciences” • Main findings: – over 3 billion base pairs – approx 30,000 genes in human beings, the same range as in mice and roundworms – 98% of the genome is “junk” DNA The Secret of Life - Discovery of DNA Structure • ..\..\..\..\Videos\Teaching\The Secret of Life -Discovery of DNA Structure.avi – Handout: Questions on the video The Secret of Life - Discovery of DNA Structure A1 Before WWII focus of genetics was on military needs. After WWII focus shifted to exploring the basis of life A2 Proteins A3 Watson was trained as a zoologist and enjoyed bird watching. Crick was a physicist A4 Linus Pauling completed with Watson & Crick. Rosalind Franklin collaborated with Watson & Crick Homework • Pg 209 Questions 4, 5 and 6
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